2-aminoethoxydiphenyl borate reveals heterogeneity in receptor activated Ca2+ discharge and store-operated Ca2+ influx
2-aminoethoxydiphenyl borate reveals heterogeneity in receptor activated Ca2+ discharge and store-operated Ca2+ influx
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DOI：
10.1054/ceca.2001.0219
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发表时间：
2001-08-01
期刊：
影响因子：
4
通讯作者：
Åkerman, KEO
中科院分区：
文献类型：
--
作者：
Kukkonen, JP;Lund, PE;Åkerman, KEO
我们用Fura-2和膜片钳技术研究了中国仓鼠卵巢K1（CHO）细胞、SH-SY 5 Y人神经母细胞瘤细胞和RBL-1大鼠嗜碱性白血病细胞的Ca ~（2+）释放和受体及钙库操纵的Ca ~（2+）内流。所谓的非竞争性IF，受体抑制剂，2-氨基乙氧基二苯基硼酸酯（2-APE）迅速阻断了主要部分的二次流入反应在CHO细胞中以可逆的方式。它还减少了响应毒胡萝卜素的Mn 2+流入。还观察到对Ca 2+释放的抑制，但这种抑制不完全，起效较慢，不可逆，并且需要较高浓度的2-APE。在RBL-1细胞中，I-CRAC活性被细胞外2-APE迅速阻断，而细胞内2-APE的有效性较低。钙池操作的Ca 2+内流仅部分被2-APB阻断。SH-SY 5 Y细胞对2-APE不敏感。RBL-1细胞的Ca ~（2+）释放对2-APE部分敏感，而SH-SY 5 Y细胞的Ca ~（2+）释放对2-APE完全不敏感。结果提示：（1）2-APB可抑制不同敏感性的IP_3受体亚型;（2）除此之外，它还通过直接的细胞外作用抑制某些钙库操纵的Ca ~（2+）通道。(C)2001年哈考特出版社有限公司
We have investigated Ca2+ release and receptor- and store-operated Ca2+ influxes in Chinese hamster ovary-K1 (CHO) cells, SH-SY5Y human neuroblastoma cells and RBL-1 rat basophilic leukemia cells using Fura-2 and patch-clamp measurements, Ca2+ release and subsequent Ni2+-sensitive, store-operated influx were induced by thapsigargin and stimulation of G protein-coupled receptors. The alleged noncompetitive IF, receptor inhibitor, 2-aminoethoxydiphenyl borate (2-APE) rapidly blocked a major part of the secondary influx response in CHO cells in a reversible manner. It also reduced Mn2+ influx in response to thapsigargin. Inhibition of Ca2+ release was also seen but this was less complete, slower in onset, less reversible, and required higher concentration of 2-APE. In RBL-I cells, I-CRAC activity was rapidly blocked by extracellular 2-APE whereas intracellular 2-APE was less effective. Store-operated Ca2+ influxes were only partially blocked by 2-APB. in SH-SY5Y cells, Ca2+ influxes were insensitive to 2-APE. Ca2+ release in RBL-1 cells was partially sensitive but in SH-SY5Y cells the release was totally resistant to 2-APE, The results suggest, that 2-APB (1) may inhibit distinct subtypes of IP3 receptors with different sensitivity, and (2) that independently of this, it also inhibits some store-operated Ca2+ channels via a direct, extracellular action. (C) 2001 Harcourt Publishers Ltd.